Optimal protection of the myocardium during cardiopulmonary bypass surgery still has the high priority. The ultimate outcome of any open-heart surgery depends on the preservation of myocardial function during the procedure. Myocardial necrosis is a frequent and deviatalizing complication for mortality and morbidity after cardiac operations. The optimal condition for myocardial preservation during surgery is not known despite of a large number of clinical and experimental studies. This is due to the reports that supported the beneficial or harmful effects of a given intervention failed to include studies to clarify the exact mechanism(s) involved in myocardial preservation. It is our goal to compare, identify, and isolate the metabolic factors and mechanisms that regulate the myocardial recovery. After the factors and mechanisms have been verified by metabolic, physiologic, and pharmacologic interventions, the beneficial interventions will be used to optimize the myocardial preservation. Isolated cardiac myocyte and isolated perfused heart under arrested condition and during reperfusion will be used to study the temperature and time dependent metabolic changes that regulate myocardial recovery. The metabolic and functional changes that associated with the beneficial effects of multiple-dose cardioplegia with substrate enhancement on cardiac functional preservation will be evaluated by related biochemical and physiological alterations. The changes, such as on glucose transport and utilization; concentrations of glycogen, high-energy-phosphates; and lactate; adenine nucleotide pool size (both mitochondrial and cytosolic); myocardial pH, myocardial edema and the accumulation and release of Na+ and Ca++ will be studied during elective cardiac arrest and reperfusion. The data resolved should be important not only for improving cardioplegic and perioperative conditions, but also in devising treatment regiments for minimizing damage and facilitating recovery in all cardiac patients.